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An 88-year-old woman underwent atrioventricular node ablation and left bundle branch pacing for atrial fibrillation. She presented to the emergency room several hours after discharge with dyspnea. An echocardiogram revealed a giant interventricular septal hematoma. The patient was successfully treated with conservative medical therapy, with eventual complete resolution of the hematoma. ( Level of Difficulty: Intermediate. )., Competing Interests: Dr. Vijayaraman has been a consultant for Abbott, Biotronik and Eaglepoint LLC; holder of a patent for HBP delivery tool and the recipient of honoraria and research and fellowship support from Medtronic; a consultant for Abbott and Biotronik; and the holder of a patent HBP delivery tool for Eaglepoint LLC. All other have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

The combination of a reducible transition metal oxide and a noble metal such as Pt often leads to active low-temperature catalysts for the preferential oxidation of CO in excess H 2 gas (PROX reaction). While CO oxidation has been investigated for such systems in model studies, the added influence of hydrogen gas, representative of PROX, remains less explored. Herein, we use ambient pressure scanning tunneling microscopy and ambient pressure X-ray photoelectron spectroscopy on a CoO x /Pt(111) planar model catalyst to analyze the active phase and the adsorbed species at the CoO x /Pt(111) interface under atmospheres of CO and O 2 with a varying partial pressure of H 2 gas. By following the evolution of the Co oxidation state as the catalyst is brought to a reaction temperature of above 150 °C, we determine that the active state is characterized by the transformation from planar CoO with Co in the 2+ state to a mixed Co 2+ /Co 3+ phase at the temperature where CO 2 production is first observed. Furthermore, our spectroscopy observations of the surface species suggest a reaction pathway for CO oxidation, proceeding from CO exclusively adsorbed on Co 2+ sites reacting with the lattice O from the oxide. Under steady state CO oxidation conditions (CO/O 2 ), the mixed oxide phase is replenished from oxygen incorporating into cobalt oxide nanoislands. In CO/O 2 /H 2 , however, the onset of the active Co 2+ /Co 3+ phase formation is surprisingly sensitive to the H 2 pressure, which we explain by the formation of several possible hydroxylated intermediate phases that expose both Co 2+ and Co 3+ . This variation, however, has no influence on the temperature where CO oxidation is observed. Our study points to the general importance of a dynamic reducibility window of cobalt oxide, which is influenced by hydroxylation, and the bonding strength of CO to the reduced oxide phase as important parameters for the activity of the system.

Pulmonary Hypertension (PH) is a pathophysiologic condition characterized by hypoxemia and right ventricular strain. Proliferation of fibroblasts, smooth muscle cells, and endothelial cells is central to the pathology of PH in animal models and in humans. Methionine aminopeptidase-2 (MetAP2) regulates proliferation in a variety of cell types including endothelial cells, smooth muscle cells, and fibroblasts. MetAP2 is inhibited irreversibly by the angiogenesis inhibitor fumagillin. We have previously found that inhibition of MetAP2 with fumagillin in bleomycin-injured mice decreased pulmonary fibrosis by selectively decreasing the proliferation of lung myofibroblasts. In this study, we investigated the role of fumagillin as a potential therapy in experimental PH. In vivo, treatment of rats with fumagillin early after monocrotaline injury prevented PH and right ventricular remodeling by decreasing the thickness of the medial layer of the pulmonary arteries. Treatment with fumagillin beginning two weeks after monocrotaline injury did not prevent PH but was associated with decreased right ventricular mass and decreased cardiomyocyte hypertrophy, suggesting a direct effect of fumagillin on right ventricular remodeling. Incubation of rat pulmonary artery smooth muscle cells (RPASMC) with fumagillin and MetAP2-targeting siRNA inhibited proliferation of RPASMC in vitro. Platelet-derived growth factor, a growth factor that is important in the pathogenesis of PH and stimulates proliferation of fibroblasts and smooth muscle cells, strongly increased expression of MetP2. By immunohistochemistry, we found that MetAP2 was expressed in the lesions of human pulmonary arterial hypertension. We propose that fumagillin may be an effective adjunctive therapy for treating PH in patients.

The efficient and correct folding of bacterial disulfide bonded proteins in vivo is dependent upon a class of periplasmic oxidoreductase proteins called DsbA, after the Escherichia coli enzyme. In the pathogenic bacterium Vibrio cholerae, the DsbA homolog (TcpG) is responsible for the folding, maturation and secretion of virulence factors. Mutants in which the tcpg gene has been inactivated are avirulent; they no longer produce functional colonisation pili and they no longer secrete cholera toxin. TcpG is thus a suitable target for inhibitors that could counteract the virulence of this organism, thereby preventing the symptoms of cholera. The crystal structure of oxidized TcpG (refined at a resolution of 2.1 A) serves as a starting point for the rational design of such inhibitors. As expected, TcpG has the same fold as E. coli DsbA, with which it shares approximately 40% sequence identity. In addition, the characteristic surface features of DsbA are present in TcpG, supporting the notion that these features play a functional role. While the overall architecture of TcpG and DsbA is similar and the surface features are retained in TcpG, there are significant differences. For example, the kinked active site helix results from a three-residue loop in DsbA, but is caused by a proline in TcpG (making TcpG more similar to thioredoxin in this respect). Furthermore, the proposed peptide binding groove of TcpG is substantially shortened compared with that of DsbA due to a six-residue deletion. Also, the hydrophobic pocket of TcpG is more shallow and the acidic patch is much less extensive than that of E. coli DsbA. The identification of the structural and surface features that are retained or are divergent in TcpG provides a useful assessment of their functional importance in these protein folding catalysts and is an important prerequisite for the design of TcpG inhibitors.